An Ad Libitum-Fed Diet That Matches the Beneficial Lifespan Effects of Caloric Restriction but Acts via Opposite Effects on the Energy-Splicing Axis.

IF 7.1 1区医学 Q1 CELL BIOLOGY

Aging Cell Pub Date : 2025-10-21 DOI:10.1111/acel.70269

Amanda E Brandon, Tamara Pulpitel, Carsten Schmitz-Peiffer, Lewin Small, Alistair M Senior, Sophie Stonehouse, Letisha Prescott, Alyssa Face, K Saiful Islam, Jenny E Gunton, Jacob George, David Raubenheimer, Gregory J Cooney, David G Le Couteur, Stephen J Simpson

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引用次数: 0

Abstract

Caloric restriction (CR) with fasting extends lifespan but is difficult to maintain in humans. Here, we compared conventional CR with periods of fasting to an ad libitum-fed low-protein, high-carbohydrate (LPHC) diet diluted 25% with non-digestible fibre. Both approaches similarly enhanced longevity and metabolic health in mice relative to a control diet. Proteomic analysis of liver tissue revealed that CR increased proteins associated with energy and mitochondrial pathways. By contrast, the LPHC diet reduced these pathways but increased the abundance of proteins associated with RNA metabolism and spliceosome pathways. These results for LPHC support the "energy-splicing resilience" axis theory of ageing. Our results suggest that ad libitum-fed diets can be designed to replicate, and potentially enhance, the geroprotective benefits of CR, albeit via different mechanisms, potentially offering a more sustainable dietary approach to longevity extension.

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一种与热量限制的有益寿命效应相匹配，但对能量拼接轴产生相反作用的自由喂养饮食。

热量限制（CR）与禁食延长寿命，但很难维持在人类。在这里，我们比较了传统的CR和禁食期间与自由喂养低蛋白，高碳水化合物（LPHC）饮食稀释25%的不可消化纤维。与对照组相比，这两种方法都同样提高了小鼠的寿命和代谢健康。肝组织的蛋白质组学分析显示，CR增加了与能量和线粒体途径相关的蛋白质。相比之下，LPHC饮食减少了这些途径，但增加了与RNA代谢和剪接体途径相关的蛋白质的丰度。这些结果支持了“能量拼接弹性”老化轴理论。我们的研究结果表明，尽管通过不同的机制，自由饲喂的饮食可以复制并潜在地增强CR的老年保护益处，可能提供一种更可持续的延长寿命的饮食方法。

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来源期刊

Aging Cell Biochemistry, Genetics and Molecular Biology-Cell Biology

自引率

2.60%

发文量

212

期刊介绍： Aging Cell is an Open Access journal that focuses on the core aspects of the biology of aging, encompassing the entire spectrum of geroscience. The journal's content is dedicated to publishing research that uncovers the mechanisms behind the aging process and explores the connections between aging and various age-related diseases. This journal aims to provide a comprehensive understanding of the biological underpinnings of aging and its implications for human health. The journal is widely recognized and its content is abstracted and indexed by numerous databases and services, which facilitates its accessibility and impact in the scientific community. These include: Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Academic Search Premier (EBSCO Publishing) Biological Science Database (ProQuest) CAS: Chemical Abstracts Service (ACS) Embase (Elsevier) InfoTrac (GALE Cengage) Ingenta Select ISI Alerting Services Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) Natural Science Collection (ProQuest) PubMed Dietary Supplement Subset (NLM) Science Citation Index Expanded (Clarivate Analytics) SciTech Premium Collection (ProQuest) Web of Science (Clarivate Analytics) Being indexed in these databases ensures that the research published in Aging Cell is discoverable by researchers, clinicians, and other professionals interested in the field of aging and its associated health issues. This broad coverage helps to disseminate the journal's findings and contributes to the advancement of knowledge in geroscience.